ENST00000428597.7:n.2449-12967C>T

Variant names:

• chr9-22083405-C-T
• rs1333040
• ENST00000428597.7:n.2449-12967C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000428597.7(CDKN2B-AS1):​n.2449-12967C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.592 in 152,000 control chromosomes in the GnomAD database, including 26,785 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.59 (26785 hom., cov: 32)
• Consequence: CDKN2B-AS1 ENST00000428597.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 188 publications found

Genes affected

CDKN2B-AS1 (HGNC:34341): (CDKN2B antisense RNA 1) This gene is located within the CDKN2B-CDKN2A gene cluster at chromosome 9p21. The gene product is a functional RNA molecule that interacts with polycomb repressive complex-1 (PRC1) and -2 (PRC2), leading to epigenetic silencing of other genes in this cluster. This region is a significant genetic susceptibility locus for cardiovascular disease, and has also been linked to a number of other pathologies, including several cancers, intracranial aneurysm, type-2 diabetes, periodontitis, Alzheimer's disease, endometriosis, frailty in the elderly, and glaucoma. Multiple alternatively processed transcript variants have been detected, some of which may take the form of circular RNA molecules (PMID:21151960). [provided by RefSeq, May 2014]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.676 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000428597.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	NR_003529.4	MANE Select	n.2449-12967C>T		intron	N/A
	CDKN2B-AS1	NR_047532.2		n.1076-8903C>T		intron	N/A
	CDKN2B-AS1	NR_047534.2		n.645-13853C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKN2B-AS1	ENST00000428597.7	TSL:1 MANE Select	n.2449-12967C>T		intron	N/A
	CDKN2B-AS1	ENST00000577551.5	TSL:1	n.534-28915C>T		intron	N/A
	CDKN2B-AS1	ENST00000580576.6	TSL:1	n.1076-8903C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.592 AC: 89859 AN: 151882 Hom.: 26775 Cov.: 32

Gnomad AFR AF: 0.616

Gnomad AMI AF: 0.577

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.585

Gnomad OTH AF: 0.631

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.592 AC: 89922 AN: 152000 Hom.: 26785 Cov.: 32 AF XY: 0.585 AC XY: 43431 AN XY: 74284

African (AFR) AF: 0.616 AC: 25552 AN: 41464

American (AMR) AF: 0.569 AC: 8693 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2426 AN: 3472

East Asian (EAS) AF: 0.695 AC: 3581 AN: 5152

South Asian (SAS) AF: 0.633 AC: 3051 AN: 4818

European-Finnish (FIN) AF: 0.453 AC: 4773 AN: 10546

Middle Eastern (MID) AF: 0.769 AC: 226 AN: 294

European-Non Finnish (NFE) AF: 0.585 AC: 39764 AN: 67956

Other (OTH) AF: 0.629 AC: 1330 AN: 2114

Alfa AF: 0.589 Hom.: 125044

Bravo AF: 0.598

Asia WGS AF: 0.655 AC: 2275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.49
DANN	Benign	0.54
PhyloP100		-1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1333040; hg19: chr9-22083404;